Publications by authors named "Volokh O"

Formation of compact dinucleosomes (CODIs) occurs after collision between adjacent nucleosomes at active regulatory DNA regions. Although CODIs are likely dynamic structures, their structural heterogeneity and dynamics were not systematically addressed. Here, single-particle Förster resonance energy transfer (spFRET) and electron microscopy were employed to study the structure and dynamics of CODIs.

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Background: Lactase persistence-the ability to digest lactose through adulthood-is closely related to evolutionary adaptations and has affected many populations since the beginning of cattle breeding. Nevertheless, the contrast initial phenotype, lactase non-persistence or adult lactase deficiency, is still observed in large numbers of people worldwide.

Methods: We performed a multiethnic genetic study of lactase deficiency on 24,439 people, the largest in Russia to date.

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Human FACT (FACT) is a multifunctional histone chaperone involved in transcription, replication and DNA repair. Curaxins are anticancer compounds that induce FACT-dependent nucleosome unfolding and trapping of FACT in the chromatin of cancer cells (c-trapping) through an unknown molecular mechanism. Here, we analyzed the effects of curaxin CBL0137 on nucleosome unfolding by FACT using spFRET and electron microscopy.

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Transcription through chromatin by RNA polymerase II (Pol II) is accompanied by the formation of small intranucleosomal DNA loops containing the enzyme (i-loops) that are involved in survival of core histones on the DNA and arrest of Pol II during the transcription of damaged DNA. However, the structures of i-loops have not been determined. Here, the structures of the intermediates formed during transcription through a nucleosome containing intact or damaged DNA were studied using biochemical approaches and electron microscopy.

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Gold nanoparticle conjugates with Vibrio cholerae antigens were synthesized. The animals were immunized with the obtained conjugates. Rabbit polyclonal antibodies to the antigens were obtained, which showed high specific activity.

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Accumulated data suggests that the gut microbiome can rapidly respond to changes in diet. Consumption of fermented dairy products (FDP) fortified with probiotic microbes may be associated with positive impact on human health. However, the extent and details of the possible impact of FDP consumption on gut community structure tends to vary across individuals.

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Nucleic acids are responsible for the storage, transfer and realization of genetic information in the cell, which provides correct development and functioning of organisms. DNA interaction with ligands ensures the safety of this information. Over the past 10 years, advances in electron microscopy and image processing allowed to obtain the structures of key DNA-protein complexes with resolution below 4Å.

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Changes of chromatin structure require participation of chromatin remodeling factors (CRFs), which are ATP-dependent multisubunit complexes that change the structure of the nucleosome without covalently modifying its components. CRFs act together with other protein factors to regulate the extent of chromatin condensation. Four CRF families are currently distinguished based on their structural and biochemical characteristics: SWI/SNF, ISWI, Mi-2/CHD, and SWR/INO80.

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Molecular dynamics simulation method was used to assess an influence of actinomycins (antibiotics used in chemotherapy for treatment of some oncology diseases) on DNA fragment elasticity. Also the efficiency of binding of actinomycin to DNA fragment was estimated. Energetic contributions of different substitutions of hydroxyl and amino-group to the phenoxazine ring of actinomycin were studied to analyze dynamic behavior and stability of antibiotic-DNA fragment complexes.

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Article Synopsis
  • The study investigates how nucleosomes, which are structures made of DNA and histones, affect the process of transcript elongation by RNA polymerase II (Pol II) during gene regulation.
  • It reveals that both interactions between DNA and histones, along with Pol II's tendency to backtrack, create a barrier that slows down or halts transcription.
  • The research suggests that nucleosomes can survive this transcription process through specific interactions between histones that stabilize their structure, ensuring proper gene regulation.
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With the method of molecular dynamics, pairs of amino acid residues have been identified on the surface of the interacting formin mDial domains: DID-DAD, which are responsible for the autoinhibition of formin, and the GTPase Rho-DID domain, and control activation. It was found that the most stable interactions are ionic interactions between Glu178 residue and Arg248 residue, as well as hydrophobic interactions between Thr175 and Phe247. The strongest interactions proved to be between the DID domain with Rho-GTPase.

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The structural characteristics of Francisella tularensis protective antigene complex (PAC) were discussed. PAC is the water-soluble antigene of outer membranes F. Tularensis with sophisticated chemical nature.

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Data on influence of Francisella tularensis C-complex preparations on formation of immunity against tularemia are presented. Study of cellular immunity characteristics as well as dynamics of antibody response was carried out on white mice and guinea pigs models. Absence of toxicity, pyrogenicity, and negative effects on immunocompetent cells in combination with protective activity points to possibility of use the C-complex as a component of a subunit vaccine.

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Technology of manufacturing of new anti-rabies immunoglobulin preparation based on F(ab')2 fragments has been developed. This preparation is characterized by low reactogenicity, increased virus-neutralizing activity and stability.

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As the result of the chromatographic separation of Y. pestis EV membrane proteins, a protein fraction with hemagglutinating activity was obtained. The isolated preparation was glycoprotein with a molecular weight of 22 kD, contained 16% of carbohydrates and exhibited thermolabile properties.

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